Affiliation:
1. Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital
2. The Second Affiliated Hospital of Chengdu Medical College
Abstract
Abstract
PURPOSE: To preliminarily clarify the mechanism of paclitaxel (PTX) resistance in cervical squamous cell carcinoma with the involvement of ZBTB5.
RESULTS: 1) Overexpression of ZBTB5 was cultured in PTX, and immunofluorescence showed that overexpression of ZBTB5 enhanced cervical squamous cell carcinoma resistance to PTX by functioning in the cell nucleus. 2) ZBTB5knockdown inhibited cell cloningand proliferation and enhanced apoptosis of cervical squamous carcinoma cells in PTX and reduced resistance to PTX in SiHa cells compared with the non-knockdown group (p < 0.05). 3) A ChIP assay was performed after overexpression of ZBTB5, which suggested that the BCL6 gene is located 395 kb from the TSS region and may be regulated by ZBTB5, which may be the promoter of BCL6. This result was consistent with that of the IPA bioinformatics analysis. 4) Further in-gel enzymatic digestion and shotgun-mass spectrometry protein identification were performed after Co-IP, and 322 differential proteins were identified in the overexpression group. Bioinformatics analysis of different proteins was conducted and 13 proteins were selected for validation: U2AF2, RBM5, ILK, ENAH, JUP, RELA/P65, SQSTM1, YY1, STIM1, Integrin alpha V, EED, SUGT1, and NFKB1. Among them, U2AF2 was successfully detected in the input, suggesting a possible interaction of ZBTB5 with U2AF2.
CONCLUSION: There is a protein–protein interaction between ZBTB5 and U2AF2, and ZBTB5 is involved in PTX resistance in cervical squamous cell carcinoma by regulating BCL6. It was hypothesized that ZBTB5 may form a transcriptional complex with U2AF2 to regulate BCL6 to affect tumor cell proliferation and participate in PTX resistance in cervical squamous cell carcinoma.
Publisher
Research Square Platform LLC
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